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Jiayan Sun,1 Yujie Li,1 Bingyu Ling,1 Qingcheng Zhu,1 Yingying Hu,2 Dingyu Tan,1 Ping Geng,1 Jun Xu31Department of Emergency, Clinical Medical College, Yangzhou University, Northern Jiangsu People’s Hospital, Yangzhou, People’s Republic of China; 2Department of Emergency, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Emergency, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, People’s Republic of ChinaBackground: High-flow nasal cannula (HFNC) oxygen therapy in acute hypoxic respiratory failure is becoming increasingly popular. However, evidence to support the use of HFNC in acute respiratory failure (ARF) with hypercapnia is limited.Methods: Chronic obstructive pulmonary disease (COPD) patients with moderate hypercapnic ARF (arterial blood gas pH 7.25–7.35, PaCO2>50mmHg) who received HFNC or non-invasive ventilation (NIV) in the intensive care uint from April 2016 to March 2018 were analyzed retrospectively. The endpoint was treatment failure, defined as either invasive ventilation, or a switch to the other study treatment (NIV for patients in the NFNC group, and vice-versa), and 28-day mortality.Results: Eighty-two COPD patients (39 in the HFNC group and 43 in the NIV group) were enrolled in this study. The mean age was 71.8±8.2 and 54 patients (65.9%) were male. The treatment failed in 11 out of 39 patients with HFNC (28.2%) and in 17 of 43 patients with NIV (39.5%) (P=0.268). No significant differences were found for 28-day mortality (15.4% in the HFNC group and 14% in the NIV group, P=0.824). During the first 24hrs of treatment, the number of nursing airway care interventions in the HFNC group was significantly less than in the NIV group, while the duration of device application was significantly longer in the HFNC group (all P

COPD is characterized by a pulmonary and systemic inflammatory process. Several authors have reported the elevation of multiple inflammatory markers in patients with COPD; however, their use in routine clinical practice has limitations. The neutrophil-to-lymphocyte ratio (NLR) is a useful and cost-effective inflammatory marker derived from routine complete blood count. We performed a systematic literature review using the PRISMA statement. Twenty-two articles were included, recruiting 7,601 COPD patients and 784 healthy controls. Compared with controls, COPD patients had significantly higher NLR values. We found a significant correlation between the NLR and clinical/functional parameters (FEV1, mMRC, and BODE index) in COPD patients. Elevation of the NLR is associated with the diagnosis of acute exacerbation of COPD (pooled data propose a cut-off value of 3.34 with a median sensitivity, specificity, and area under the curve of 80%, 86%, and 0.86, respectively). Additionally, increased NLR is also associated with the diagnosis of a bacterial infection in exacerbated patients, with a cut-off value of 7.30, although with a low sensitivity and specificity. The NLR is an independent predictor of in-hospital and late mortality after exacerbation. In conclusion, the NLR could be a useful marker in COPD patients; however, further studies are needed to better identify the clinical value of the NLR.

Marc Miravitlles,1 Jéssica Montero-Caballero,2 Frank Richard,2 Salud Santos,3 Juan Luis Garcia-Rivero,4 Francisco Ortega,5 Xavier Ribera61Pneumology Department, Hospital Universitari Vall d’Hebron, Ciber de Enfermedades Respiratorias (CIBERES), Barcelona, Spain; 2Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany; 3Pulmonology Department, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Ciber de Enfermedades Respiratorias (CIBERES), Barcelona, Spain; 4Pneumology Department, Hospital de Laredo, Cantabria, Spain; 5Pneumology Department, Hospital Virgen del Rocío, Sevilla, Spain; 6Boehringer Ingelheim Pharma GmbH & Co KG, Barcelona, Spain Abstract: Delivery of inhaled medications via an inhaler device underpins the effectiveness of treatment for patients with chronic obstructive pulmonary disease (COPD). Correct inhaler technique among patients is also a predictor of achieving treatment compliance and adherence. Reporting of patient satisfaction with inhalers is therefore gaining increasing attention and is now recognized as an important patient-reported outcome in clinical trials involving patients with COPD or asthma. In this cross-sectional study, we use the validated Patient Satisfaction and Preference Questionnaire (PASAPQ) to assess the handling and satisfaction for Respimat® Soft Mist™ Inhaler (SMI) compared with the Breezhaler® dry powder inhaler (DPI) among patients with COPD in Spain. Patients were already assigned to therapy with either SPIRIVA® (tiotropium) Respimat® or with Hirobriz®/Onbrez®/Oslif® (indacaterol) Breezhaler® for at least 3 but not more than 6 months before completing the PASAPQ at a single visit to the study site. The primary endpoint of the trial was the mean total PASAPQ score. Secondary endpoints were the performance score domain of the PASAPQ, the convenience score domain of the PASAPQ, and the overall satisfaction score of the PASAPQ. For the primary endpoint, the mean PASAPQ total score in the Respimat® and Breezhaler® groups was 80.7 and 79.9, respectively (difference of 0.8, 95% confidence interval [CI] −2.9 to 4.5; P=0.67). The mean total performance scores were 82.5 and 78.2 (difference of 4.3, 95% CI −0.3 to 8.9; P=0.06), and the mean total convenience scores were 78.6 and 81.9 (difference of −3.3, 95% CI −7.0 to 0.4; P=0.08) for the Respimat® and Breezhaler® groups, respectively. Patients gave the Respimat® SMI and the Breezhaler® DPI overall satisfaction PASAPQ scores of 6.0 and 5.9, respectively, which shows that patients were satisfied with these inhalers.Keywords: COPD, Respimat®, Breezhaler®, inhaler, handling

Cristina Esquinas,1,2 Sabina Janciauskiene,3 Ricardo Gonzalo,4 Gemma Mas de Xaxars,4 Beata Olejnicka,5 Irene Belmonte,6 Miriam Barrecheguren,1 Esther Rodriguez,1 Alexa Nuñez,1 Francisco Rodriguez-Frias,6 Marc Miravitlles1 1Pneumology Department, University Hospital Vall d’Hebron, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, 2Public Health, Mental, Maternal and Child Health Nursing Department, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; 3Department of Respiratory Medicine, Hannover Medical School, BREATH, German Center for Lung Research (DZL), Hannover, Germany; 4Statistics and Bioinformatics Unit (UEB), Vall d’Hebron Research Institute (VHIR), Barcelona, Spain; 5Department of Experimental Medical Science, Lund University, Lund, Sweden; 6Biochemistry Department, University Hospital Vall d’Hebron, Barcelona, Spain Introduction: COPD has complex etiologies involving both genetic and environmental determinants. Among genetic determinants, the most recognized is a severe PiZZ (Glu342Lys) inherited alpha1-antitrypsin deficiency (AATD). Nonetheless, AATD patients present a heterogeneous clinical evolution, which has not been completely explained by sociodemographic or clinical factors. Here we performed the gene expression profiling of blood cells collected from mild and severe COPD patients with PiZZ AATD. Our aim was to identify differences in messenger RNA (mRNA) and microRNA (miRNA) expressions that may be associated with disease severity. Materials and methods: Peripheral blood mononuclear cells from 12 COPD patients with PiZZ AATD (6 with severe disease and 6 with mild disease) were used in this pilot, high-throughput microarray study. We compared the cellular expression levels of RNA and miRNA of the 2 groups, and performed functional and enrichment analyses using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene-ontology (GO) terms. We also integrated the miRNA and the differentially expressed putative target mRNA. For data analyses, we used the R statistical language R Studio (version 3.2.5). Results: The severe and mild COPD–AATD groups were similar in terms of age, gender, exacerbations, comorbidities, and use of augmentation therapy. In severe COPD–AATD patients, we found 205 differentially expressed genes (DEGs) (114 upregulated and 91 downregulated) and 28 miRNA (20 upregulated and 8 downregulated) compared to patients with mild COPD–AATD disease. Of these, hsa-miR-335-5p was downregulated and 12 target genes were involved in cytokine signaling, MAPK/mk2, JNK signaling cascades, and angiogenesis were much more highly expressed in severe compared with mild patients. Conclusions: Despite the small sample size, we identified downregulated miRNA (hsa-miR-335) and the activation of pathways related to inflammation and angiogenesis on comparing patients with severe vs mild COPD–AATD. Nonetheless, our findings warrant further validation in large studies. Keywords: alpha1-antitrypsin deficiency, COPD, gene expression, miRNAs, integrative analysis

Guoping Hu,1 Yankui Wu,2 Yumin Zhou,3 Zelong Wu,1 Liping Wei,1 Yuqun Li,1 GongYong Peng,3 Weiqiang Liang,1 Pixin Ran3 1Department of Respiratory Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 2Department of Respiratory Disease of People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Zhuang Autonomous Region, 3Guangzhou Institute of Respiratory Disease, State Key Lab of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China Background and objective: Serum D-dimer is elevated in respiratory disease. The objective of our study was to investigate the effect of D-dimer on in-hospital and 1-year mortality after acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Methods: Upon admission, we measured 343 AECOPD patients’ serum D-dimer levels and arterial blood gas analysis, and recorded their clinical characteristics. The level of D-dimer that discriminated survivors and non-survivors was determined using a receiver operator curve (ROC). The risk factors for in-hospital mortality were identified through univariate analysis and multiple logistic regression analyses. To evaluate the predictive role of D-dimer for 1-year mortality, univariate and multivariate Cox regression analyses were performed. Results: In all, 28 patients died, and 315 patients survived in the in-hospital period. The group of dead patients had lower pH levels (7.35±0.11 vs 7.39±0.05, P

Alicia Lacoma1,4, Cristina Prat1,4, Felipe Andreo2,4, Luis Lores3, Juan Ruiz-Manzano2,4, Vicente Ausina1,4, Jose Domínguez1,41Servei de Microbiologia, 2Servei de Pneumologia, Hospital Universitari Germans Trias i Pujol, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain; 3Servei de Pneumologia, Hospital de Sant Boi, Sant Boi de Llobregat, Spain; 4CIBER Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, SpainObjective: The identification of biological markers in order to assess different aspects of COPD is an area of growing interest. The objective of this study was to investigate whether levels of procalcitonin (PCT), C-reactive protein (CRP), and neopterin in COPD patients could be useful in identifying the etiological origin of the exacerbation and assessing its prognosis.Methods: We included 318 consecutive COPD patients: 46 in a stable phase, 217 undergoing an exacerbation, and 55 with pneumonia. A serum sample was collected from each patient at the time of being included in the study. A second sample was also collected 1 month later from 23 patients in the exacerbation group. We compared the characteristics, biomarker levels, microbiological findings, and prognosis in each patient group. PCT and CRP were measured using an immunofluorescence assay. Neopterin levels were measured using a competitive immunoassay.Results: PCT and CRP showed significant differences among the three patient groups, being higher in patients with pneumonia, followed by patients with exacerbation (P < 0.0001). For the 23 patients with paired samples, PCT and CRP levels decreased 1 month after the exacerbation episode, while neopterin increased. Neopterin showed significantly lower levels in exacerbations with isolation of pathogenic bacteria, but no differences were found for PCT and CRP. No significant differences were found when comparing biomarker levels according to the Gram result: PCT (P = 0.191), CRP (P = 0.080), and neopterin (P = 0.109). However, median values of PCT and CRP were high for Streptococcus pneumoniae, Staphylococcus aureus, and enterobacteria. All biomarkers were higher in patients who died within 1 month after the sample collection than in patients who died later on.Conclusions: According to our results, biomarker levels vary depending on the clinical status. However, the identification of the etiology of infectious exacerbation by means of circulating biomarkers is encouraging, but its main disadvantage is the absence of a microbiological gold standard, to definitively demonstrate their value. High biomarker levels during an exacerbation episode correlate with the short-term prognosis, and therefore their measurement can be useful for COPD management.Keywords: C-reactive protein, exacerbation, neopterin, procalcitonin, prognosis

Marc Miravitlles,1 Patricia García-Sidro,2 Alonso Fernández-Nistal,3 María Jesús Buendía,4 María José Espinosa de losMonteros,5 Cristina Esquinas,1 Jesús Molina6 1Pneumology Department, Hospital Universitari Vall d’Hebron, Ciber de Enfermedades Respiratorias, Barcelona, 2Pneumology Unit, Hospital de la Plana, Villareal, 3Medical Department, Takeda Farmacéutica España S.A., Madrid, 4Pneumology Department, Hospital Universitario Infanta Leonor, Madrid, 5Pneumology Department, Hospital Universitario Virgen de la Salud, Toledo, 6Centro de Salud “Francia”, Fuenlabrada, Madrid, Spain Introduction: Chronic obstructive pulmonary disease (COPD) exacerbations have a negative impact on the quality of life of patients and the evolution of the disease. We have investigated the prognostic value of several health-related quality of life questionnaires to predict the appearance of a composite event (new ambulatory or emergency exacerbation, hospitalization, or death) over a 1-year follow-up.Methods: This was a multicenter, prospective, observational study. Patients completed four questionnaires after recovering from an exacerbation (COPD Assessment Test [CAT], a Clinical COPD Questionnaire [CCQ], COPD Severity Score [COPDSS], and Airways Questionnaire [AQ20]). Patients were followed-up until the appearance of the composite event or for 1 year, whichever came first.Results: A total of 497 patients were included in the study. The majority of them were men (89.7%), with a mean age of 68.7 (SD 9.2) years, and a forced expiratory volume in 1 second of 47.1% (SD 17.5%). A total of 303 (61%) patients experienced a composite event. Patients with an event had worse mean scores of all questionnaires at baseline compared to patients without event: CAT=12.5 vs 11.3 (P=0.028); CCQ=2.2 vs 1.9 (P=0.013); COPDSS=12.3 vs 10.9 (P=0.001); AQ20=8.3 vs 7.5 (P=0.048). In the multivariate analysis, only previous history of exacerbations and CAT score ≥13.5 were significant risk factors for the composite event. A CAT score ≥13.5 increased the predictive value of previous exacerbations with an area under the receiver operating characteristic curve of 0.864 (95% CI: 0.829–0.899; P=0.001).Conclusion: The predictive value of previous exacerbations significantly increased only in one of the four trialled questionnaires, namely in the CAT questionnaire. However, previous history of exacerbations was the strongest predictor of the composite event. Keywords: COPD, CAT, CCQ, COPDSS, AQ20, exacerbations

Background: Retrospective studies based on clinical data and without spirometric confirmation suggest a poorer prognosis of patients with ischemic heart disease (IHD) and chronic obstructive pulmonary disease (COPD) following percutaneous coronary intervention (PCI). The impact of undiagnosed COPD in these patients is unknown. We aimed to evaluate the prognostic impact of COPD – previously or newly diagnosed – in patients with IHD treated with PCI. Methods: Patients with IHD confirmed by PCI were consecutively included. After PCI they underwent forced spirometry and evaluation for cardiovascular risk factors. All-cause mortality, new cardiovascular events, and their combined endpoint were analyzed. Results: A total of 133 patients (78%) male, with a mean (SD) age of 63 (10.12) years were included. Of these, 33 (24.8%) met the spirometric criteria for COPD, of whom 81.8% were undiagnosed. IHD patients with COPD were older, had more coronary vessels affected, and a greater history of previous myocardial infarction. Median follow-up was 934 days (interquartile range [25%–75%]: 546–1,160). COPD patients had greater mortality (P=0.008; hazard ratio [HR]: 8.85; 95% confidence interval [CI]: 1.76–44.47) and number of cardiovascular events (P=0.024; HR: 1.87; 95% CI: 1.04–3.33), even those without a previous diagnosis of COPD (P=0.01; HR: 1.78; 95% CI: 1.12–2.83). These differences remained after adjustment for sex, age, number of coronary vessels affected, and previous myocardial infarction (P=0.025; HR: 1.83; 95% CI: 1.08–3.1), The CATEPOC study was supported in part by Menarini Spain

Karina Portillo,1 Yolanda Torralba,1,2 Isabel Blanco,1,2 Felip Burgos,1,2 Roberto Rodriguez-Roisin,1,2 Jose Rios,3 Josep Roca,1,2 Joan A Barberà1,21Department of Pulmonary Medicine, Hospital Clínic-Institut d’Investigacions Biomèdiques August Pi iSunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; 2Centro de Investigación Biomédica en Redde Enfermedades Respiratorias (CIBERES), Madrid, Spain; 3Biostatistics and Data Management Core Facility, Hospital Clínic-Institut d’Investigacions Biomèdiques AugustPi iSunyer (IDIBAPS), Biostatistics Unit, School of Medicine, Universitat Autònoma deBarcelona, Barcelona, SpainIntroduction: Few data are available in regards to the prevalence of pulmonary hypertension (PH) in the broad spectrum of COPD. This study was aimed at assessing the prevalence of PH in a cohort of COPD patients across the severity of airflow limitation, and reporting the hemodynamic characteristics at rest and during exercise.Methods: We performed a retrospective analysis on COPD patients who underwent right-heart catheterization in our center with measurements obtained at rest (n=139) and during exercise (n=85). PH was defined as mean pulmonary artery pressure (mPAP) ≥25 mmHg and pulmonary capillary wedge pressure 3.Results: PH was present in 25 patients (18%). According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, PH prevalence in GOLD 2 was 7% (3 patients); 25% (14 patients) in GOLD 3; and 22% (8 patients) in GOLD 4. Severe PH (mPAP ≥35 mmHg) was identified in four patients (2.8%). Arterial partial oxygen pressure was the outcome most strongly associated with PH (r=-0.29, P

Jose Luis Lopez-Campos,1,2,* Alberto Fernandez-Villar,3,* Carmen Calero-Acuña,1 Cristina Represas-Represas,3 Cecilia Lopez-Ramírez,1 Virginia Leiro Fernández,3 Juan Jose Soler-Cataluña,2,4 Ricard Casamor5 On behalf of the On-Sint study group 1Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio/Universidad de Sevilla, Sevilla, Spain; 2CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain; 3Servicio de Neumología, Instituto de Investigación Biomédica de Vigo (IBIV), Complexo Hospitalario de Vigo, Vigo, Spain; 4Servicio de Neumología Hospital Arnau de Vilanova, Valencia, Spain; 5Departamento Médico de Novartis Farmacéutica, Barcelona, Spain *These authors contributed equally to this work Background: The COPD Assessment Test (CAT) has been recently developed to quantify COPD impact in routine practice. However, no relationship with other measures in the Global Initiative for Obstructive Lung Disease (GOLD) strategy has been evaluated. The present study aimed to evaluate the relationship of the CAT with other GOLD multidimensional axes, patient types, and the number of comorbidities.Methods: This was a cross-sectional analysis of the Clinical presentation, diagnosis, and course of chronic obstructive pulmonary disease (On-Sint) study. The CAT score was administered to all participants at the inclusion visit. A GOLD 2011 strategy consisting of modified Medical Research Council scale (MRC) scores was devised to study the relationship between the CAT, and GOLD 2011 axes and patient types. The relationship with comorbidities was assessed using the Charlson comorbidity index, grouped as zero, one to two, and three or more.Results: The CAT questionnaire was completed by 1,212 patients with COPD. The CAT maintained a relationship with all the three axes, with a ceiling effect for dyspnea and no distinction between mild and moderate functional impairment. The CAT score increased across GOLD 2011 patient types A–D, with similar scores for types B and C. Within each GOLD 2011 patient type, there was a considerably wide distribution of CAT values.Conclusion: Our study indicates a correlation between CAT and the GOLD 2011 classification axes as well as the number of comorbidities. The CAT score can help clinicians, as a complementary tool to evaluate patients with COPD within the different GOLD patient types. Keywords: chronic obstructive pulmonary diseases, multidimensional evaluation, comorbidities

Josep Darbà,1 Gabriela Ramírez,2 Antoni Sicras,3 Pablo Francoli,4 Saku Torvinen,5 Rainel Sánchez-de la Rosa4 1Department of Economics, Universitat de Barcelona, 2BCN Health Economics and Outcomes Research SL, 3Dirección de Planificación, Badalona Serveis Assistencials, SA, Barcelona, 4Medical Department, TEVA Pharmaceutical, Madrid, Spain; 5Market Access Department, TEVA Pharmaceutical Europe BV, Amsterdam, the Netherlands Objective: This study aims to identify factors associated with poor adherence to COPD treatment in patients receiving a fixed-dose combination (FDC) of inhaled corticosteroids and long-acting β2-agonist (ICS/LABA), focusing on the importance of inhaler devices.Methods: We conducted a retrospective and multicenter study based on a review of medical registries between 2007 and 2012 of COPD patients (n=1,263) treated with ICS/LABA FDC, whose medical devices were either dry powder inhalers (DPIs) or pressurized metered-dose inhalers (pMDI). Medication adherence included persistence outcomes through 18months and medication possession ratios. Data on exacerbations, comorbidities, demographic characteristics, and health care resource utilization were also included as confounders of adherence.Results: The analyses revealed that COPD patients whose medication wasdelivered through a DPI were less likely to have medication adherence compared to patients with pMDI, after adjusting for confounding factors, especially active ingredients. Younger groups of patients were less likely to be adherent compared to the oldest group. Smoker men were less likely to be adherent compared to women and non-smokers. Comorbidities decreased the probability of treatment adherence. Those patients that visited their doctor once a month were more likely to adhere to their medication regimen; however, suboptimal adherence was more likely to occur among those patients who visited more than three times per month their doctor. We also found that worsening of COPD is negatively associated with adherence.Conclusion: According to this study, inhaler devices influence patients’ adherence to long-term COPD medication. We also found that DPIs delivering ICS/LABA FDC had a negative impact on adherence. Patients’ clinic and socioeconomic characteristics were associated with adherence. Keywords: adherence, inhaler technique, medication possession ratio (MPR), dry powder inhalers (DPIs), pressurized metered-dose inhalers (pMDIs), persistence